Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome.
Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome.
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DOI：
10.1371/journal.pone.0142843
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wada T
中科院分区：
文献类型：
--
作者：
Okumura T;Furuichi K;Higashide T;Sakurai M;Hashimoto S;Shinozaki Y;Hara A;Iwata Y;Sakai N;Sugiyama K;Kaneko S;Wada T
肾缺损综合征（RCS）的特征是肾脏异常和视神经缺损。PAX 2突变有助于RCS。然而，大约一半的RCS患者PAX 2基因没有突变。为了研究PAX 2和25个候选基因突变的发生率和影响，使用下一代序列分析筛选患者基因，并使用桑格测序确认候选突变。评价突变与临床表现的相关性。30例患者，包括26例RCS患者（两个五人家庭和两个家庭，19例散发病例）和4例仅视神经缺损的对照病例，在本研究中进行了评价。使用桑格测序证实了21名先证者中的6个PAX 2突变[28%; 2个在家族队列中（n = 5和n = 2），4个在19名散发性疾病患者中]，包括4个新突变。此外，还确认了其他四种序列变体（CHD 7，SALL 4，KIF 26 B和SIX 4），包括潜在致病性的新型KIF 26 B突变。PAX 2突变患者的肾功能和蛋白尿比没有突变的患者更严重。此外，PAX 2基因突变患者的缺损评分显著较高。五分之三的PAX 2突变患者患有肾活检诊断的局灶节段性肾小球硬化症（FSGS）。这项研究的结果确定了PAX 2的几个新突变，以及另外四个基因的序列变体，包括KIF 26 B中的一个新的潜在致病突变，该突变可能在RCS的发病机制中发挥作用。
Renal coloboma syndrome (RCS) is characterized by renal anomalies and optic nerve colobomas. PAX2 mutations contribute to RCS. However, approximately half of the patients with RCS have no mutation in PAX2 gene. To investigate the incidence and effects of mutations of PAX2 and 25 candidate genes, patient genes were screened using next-generation sequence analysis, and candidate mutations were confirmed using Sanger sequencing. The correlation between mutations and clinical manifestation was evaluated. Thirty patients, including 26 patients (two families of five and two, 19 sporadic cases) with RCS, and 4 optic nerve coloboma only control cases were evaluated in the present study. Six PAX2 mutations in 21 probands [28%; two in family cohorts (n = 5 and n = 2) and in 4 out of 19 patients with sporadic disease] including four novel mutations were confirmed using Sanger sequencing. Moreover, four other sequence variants (CHD7, SALL4, KIF26B, and SIX4) were also confirmed, including a potentially pathogenic novel KIF26B mutation. Kidney function and proteinuria were more severe in patients with PAX2 mutations than in those without the mutation. Moreover, the coloboma score was significantly higher in patients with PAX2 gene mutations. Three out of five patients with PAX2 mutations had focal segmental glomerulosclerosis (FSGS) diagnosed from kidney biopsies. The results of this study identify several new mutations of PAX2, and sequence variants in four additional genes, including a novel potentially pathogenic mutation in KIF26B, which may play a role in the pathogenesis of RCS.